USMLE Physiology Syllabus

Outline the renin-angiotensin-aldosterone system (RAAS) cascade.

Low BP/low renal perfusion triggers renin from juxtaglomerular cells. Renin converts angiotensinogen to angiotensin I; ACE (lung) converts angiotensin I to angiotensin II. Angiotensin II causes vasoconstriction and stimulates aldosterone release, increasing $\ce{Na+}$/water retention.

What are the major actions of angiotensin II?

Potent vasoconstriction (raises TPR), stimulates aldosterone (increases $\ce{Na+}$ reabsorption), stimulates ADH release and thirst, increases proximal tubule $\ce{Na+}$/$\ce{H2O}$ reabsorption, and constricts efferent arteriole to maintain GFR.

What stimulates release of atrial natriuretic peptide (ANP) and what are its effects?

ANP is released from atrial myocytes in response to atrial stretch (increased blood volume/pressure). It promotes vasodilation, increases GFR, and causes natriuresis (Na+/water excretion), lowering blood volume and pressure — opposing RAAS.

State the resting membrane potential of a typical neuron and the ion primarily responsible for it.

The resting membrane potential is approximately $-70\ \text{mV}$. It is set mainly by high resting permeability to $\ce{K+}$, driving the membrane potential toward the potassium equilibrium potential.

Write the Nernst equation for the equilibrium potential of an ion.

$$E_{ion} = \frac{RT}{zF}\ln\frac{[\text{ion}]_{out}}{[\text{ion}]_{in}}$$ At body temperature for a monovalent cation this simplifies to $E \approx 61 \times \log_{10}\frac{[\text{ion}]_{out}}{[\text{ion}]_{in}}\ \text{mV}$.

List the sequential phases of a neuronal action potential and the ion channels involved in each.

1) Depolarization: voltage-gated $\ce{Na+}$ channels open, $\ce{Na+}$ enters. 2) Repolarization: $\ce{Na+}$ channels inactivate and voltage-gated $\ce{K+}$ channels open, $\ce{K+}$ exits. 3) Hyperpolarization (undershoot): $\ce{K+}$ channels remain open transiently.

Distinguish the absolute refractory period from the relative refractory period.

Absolute refractory period: no new action potential can be generated regardless of stimulus, due to inactivated $\ce{Na+}$ channels. Relative refractory period: a larger-than-normal stimulus can trigger an action potential, occurring during hyperpolarization when $\ce{K+}$ conductance is high.

What role does the $\ce{Na+/K+}$-ATPase play in maintaining the resting potential?

The $\ce{Na+/K+}$-ATPase pumps 3 $\ce{Na+}$ out and 2 $\ce{K+}$ in per ATP, maintaining the concentration gradients ($\ce{Na+}$ high outside, $\ce{K+}$ high inside). It is electrogenic, contributing slightly to the negative resting potential.

Explain how myelination and saltatory conduction increase conduction velocity.

Myelin insulates the axon, reducing membrane capacitance and current leak. Action potentials regenerate only at the nodes of Ranvier (where Na+ channels cluster), so the impulse 'jumps' node to node (saltatory conduction), greatly increasing conduction velocity.

Describe the sequence of events in synaptic transmission at a chemical synapse.

An action potential depolarizes the presynaptic terminal, opening voltage-gated $\ce{Ca^2+}$ channels. $\ce{Ca^2+}$ influx triggers vesicle fusion and neurotransmitter release into the cleft. Neurotransmitter binds postsynaptic receptors, causing an excitatory or inhibitory postsynaptic potential.

What is the essential role of calcium in neurotransmitter release?

$\ce{Ca^2+}$ entering through voltage-gated calcium channels binds synaptotagmin on synaptic vesicles, triggering SNARE-mediated fusion of vesicles with the presynaptic membrane and exocytosis of neurotransmitter.

Contrast an EPSP with an IPSP.

An EPSP (excitatory postsynaptic potential) depolarizes the membrane toward threshold, typically via $\ce{Na+}$/$\ce{Ca^2+}$ influx (e.g., glutamate). An IPSP (inhibitory postsynaptic potential) hyperpolarizes/stabilizes the membrane, typically via $\ce{Cl-}$ influx or $\ce{K+}$ efflux (e.g., GABA, glycine).

Differentiate temporal summation from spatial summation of synaptic potentials.

Temporal summation: rapid successive EPSPs from a single presynaptic neuron add together over time. Spatial summation: EPSPs from multiple presynaptic neurons at different locations add together simultaneously. Both can bring the postsynaptic cell to threshold.

How is acetylcholine removed from the synaptic cleft, and why is this significant?

Acetylcholine is hydrolyzed by acetylcholinesterase into acetate and choline. This rapid degradation terminates the signal. Acetylcholinesterase inhibitors (e.g., organophosphates, neostigmine) prolong ACh action, causing cholinergic excess.

State the Weber-Fechner law relating stimulus intensity to perceived sensation.

The Weber-Fechner law states that perceived sensation intensity is proportional to the logarithm of the stimulus intensity: $$P = k \ln\frac{S}{S_0}$$ This allows a wide dynamic range of stimulus detection.

Define receptor adaptation and contrast tonic (slow) versus phasic (fast) receptors.

Adaptation is a decline in receptor firing during a sustained stimulus. Tonic receptors adapt slowly and signal stimulus duration/intensity (e.g., muscle spindles, nociceptors). Phasic receptors adapt rapidly and signal change/onset (e.g., Pacinian corpuscles).

List the four mechanoreceptors of glabrous skin and the stimulus each detects.

Meissner corpuscles (light touch, fast-adapting), Merkel discs (pressure/texture, slow-adapting), Pacinian corpuscles (vibration/deep pressure, fast-adapting), and Ruffini endings (skin stretch, slow-adapting).

Trace the pathway of the dorsal column-medial lemniscus system.

It carries fine touch, vibration, and proprioception. First-order neurons ascend ipsilaterally in the dorsal columns to the medulla (nucleus gracilis/cuneatus), second-order neurons decussate and ascend as the medial lemniscus to the VPL of the thalamus, and third-order neurons project to the primary somatosensory cortex.

Trace the pathway of the spinothalamic tract and the modalities it carries.

The spinothalamic tract carries pain and temperature. First-order neurons synapse in the dorsal horn; second-order neurons decussate at the spinal cord level (anterior white commissure) and ascend contralaterally to the VPL of the thalamus; third-order neurons project to the somatosensory cortex.

How does the cochlea encode sound frequency (tonotopy)?

Sound frequency is encoded by place along the basilar membrane. The stiff, narrow base responds to high frequencies; the flexible, wide apex responds to low frequencies. This tonotopic organization is preserved up to the auditory cortex.

In the phototransduction cascade, what happens to rods in the dark versus in light?

In the dark, high cGMP keeps $\ce{Na+}$ channels open (depolarized 'dark current'), releasing glutamate. Light activates rhodopsin, which activates transducin and phosphodiesterase, lowering cGMP, closing $\ce{Na+}$ channels, and hyperpolarizing the rod, decreasing glutamate release.

Define glomerular filtration rate (GFR) and give its normal value.

GFR is the volume of plasma filtered from the glomerular capillaries into Bowman's capsule per unit time. Normal GFR is approximately $120\text{–}125\ \text{mL/min}$ (about $180\ \text{L/day}$).

Write the equation for the net filtration pressure and GFR across the glomerulus.

$$GFR = K_{f}\left[(P_{GC} - P_{BS}) - (\pi_{GC} - \pi_{BS})\right]$$ where $P_{GC}$ is glomerular capillary hydrostatic pressure, $P_{BS}$ is Bowman's space hydrostatic pressure, $\pi_{GC}$ is glomerular oncotic pressure, and $\pi_{BS} \approx 0$.

How do afferent versus efferent arteriole constriction each affect GFR?

Afferent arteriole constriction decreases glomerular hydrostatic pressure, lowering GFR and RPF. Efferent arteriole constriction increases glomerular hydrostatic pressure, increasing GFR while decreasing RPF (raising filtration fraction). Angiotensin II preferentially constricts the efferent arteriole.

Why is inulin used to measure GFR, and what makes an ideal GFR marker?

Inulin is freely filtered, and neither reabsorbed nor secreted by the tubules, so the amount filtered equals the amount excreted. Thus its clearance equals GFR: $$GFR = \frac{U_{in} \times V}{P_{in}}$$

Write the general renal clearance equation and define filtration fraction.

Clearance: $$C_{x} = \frac{U_{x} \times V}{P_{x}}$$ Filtration fraction is the fraction of renal plasma flow filtered: $$FF = \frac{GFR}{RPF}$$ (normally about $20\%$; PAH clearance estimates RPF).

What is transported in the proximal convoluted tubule (PCT), and what fraction of filtered Na+ is reabsorbed there?

The PCT reabsorbs about $65\text{–}67\%$ of filtered $\ce{Na+}$ and water, and nearly all glucose, amino acids, and $\ce{HCO3-}$. It is the main site of isosmotic reabsorption and generates $\ce{NH3}$ for acid excretion.

Describe the transport function of the thick ascending limb of the loop of Henle.

The thick ascending limb reabsorbs $\ce{Na+}$, $\ce{K+}$, and $\ce{Cl-}$ via the $\ce{Na+/K+/2Cl-}$ (NKCC2) cotransporter (blocked by loop diuretics). It is impermeable to water, so it dilutes tubular fluid and contributes to the medullary osmotic gradient.

Compare the actions of aldosterone and ADH in the collecting duct.

Aldosterone acts on principal cells to increase $\ce{Na+}$ reabsorption (via ENaC) and $\ce{K+}$/$\ce{H+}$ secretion. ADH (vasopressin) inserts aquaporin-2 channels into the apical membrane, increasing water reabsorption and concentrating the urine.

State the Henderson-Hasselbalch equation for the bicarbonate buffer system and normal arterial pH.

$$pH = 6.1 + \log_{10}\frac{[\ce{HCO3-}]}{0.03 \times P_{CO_2}}$$ Normal arterial pH is $7.35\text{–}7.45$, with $[\ce{HCO3-}] \approx 24\ \text{mEq/L}$ and $P_{CO_2} \approx 40\ \text{mmHg}$.

Classify the four primary acid-base disorders by pH, $P_{CO_2}$, and $\ce{HCO3-}$, and give the expected respiratory compensation for metabolic acidosis (Winter's formula).

Metabolic acidosis: low pH, low $\ce{HCO3-}$. Metabolic alkalosis: high pH, high $\ce{HCO3-}$. Respiratory acidosis: low pH, high $P_{CO_2}$. Respiratory alkalosis: high pH, low $P_{CO_2}$. Winter's formula for metabolic acidosis: $$P_{CO_2} = 1.5\,[\ce{HCO3-}] + 8 \pm 2$$